The present invention relates to deep brain stimulation (DBS) systems, and more particularly to a DBS system that utilizes a multichannel implantable pulse generator (IPG) small enough to be implanted directly in the cranium of the patient.
More than a decade ago, a single channel implantable pulse generator (IPG) was developed for the purpose of stimulating the spinal cord to treat chronic and intractable pain. Over the years, more and more applications for implantable systems that could deliver electrical stimulation to neural tissues were discovered, including the stimulation of structures deep within the brain controlling movement. For each of these applications, the single channel IPG with it's single channel stimulator was placed into a new package, sometimes with a new name, sometimes with a variation in its electrode, and provided as a new product, each time using the same electronics, power systems, telemetry methods, cumbersome programming methods, and often the same leadwires and surgical tools for those devices. So, while the technology offered through the single channel device was not as sophisticated as what it could deliver, it was still the best available technology, and as a result systems have existed that may not have been adequate for the job, but were better than no systems as all.
There is now a recognition that patients suffering from Parkinson's Disease, essential tremor, and other movement disorders, need better devices to treat their conditions. Such devices need to last many times longer, need to reduce the surgical time required for their implantation, and need to better address the problems for which they are applied in patients. Moreover, such devices should preferably be designed for the surgical location of the device and the structures to be stimulated, rather than just be a re-labeled system designed for another application altogether and simply marketed for a new application.
Thus, while single channel DBS systems are known in the art, such systems suffer from numerous defects and serious deficiencies.
For example, one system used today for DBS applications utilizes an implantable pulse generator powered by a primary battery (non-rechargeable), originally designed for spinal cord stimulation. The pulse generator is large and must be implanted in the shoulder region, thereby requiring long leads and an arduous surgical procedure of tunneling in order to interconnect the leads with the pulse generator and in order to place the leads and electrodes in the desired location in contact with brain tissue. For many patients with aggressive stimulation parameter settings, the lifetime of the primary battery is very short, thus requiring frequent replacement surgeries.
An alternative to the primary battery powered device is an RF-powered device which requires that the patient wear an antenna coil over the site of the implant and carry an external transmitter/controller.
When bilateral stimulation is required using existing DBS devices, which occurs often, two complete, independent pulse generators, including separate lead wires and electrode systems must presently be implanted.
Patient controllers for use with existing systems require that the patient controller be held directly over the implant site for the transfer of telemetry commands. This makes use of such patient controller for an implant site on the cranium extremely difficult, if not impossible. Additionally, use of such a patient controller with a shoulder-located stimulator is similarly deficient.
It is thus seen that numerous problems and deficiencies are present with existing DBS systems.
A brief review of the literature follows which describes the work of various clinicians and researchers in the application of DBS and early chronic cerebellar stimulation (CCS) for the treatment of pain and movement disorders. Basic research and issues with the technology of electrical stimulation are discussed.
CCS and DBS Early Work
Cooper, I, in various publications made in 1978, 1980, 1981, and 1984, (see, e.g., Cooper, I: Historical review of cerebellar stimulation. Cerebellar Stimulation for Spasticity and Seizures: 3-8, 1984 by Davis, R and Bloedel, J), reported that chronic cerebellar stimulation (CCS) and deep brain stimulation (DBS) were employed to reverse some of the symptoms of spasticity, hemiparesis, tremor, dystonia and torticollis by prosthetic mobilization of CNS inhibitory mechanisms in the cerebral cortex and thalamus. Again, in 1985, Cooper demonstrated that the long term chronic stimulation of the brain has resulted in no harmful effects in any case while at the same time demonstrating effectiveness (see Cooper et al., “The effect of chronic stimulation of cerebellum and thalamus upon neurophysiology and neurochemistry of cerebral cortex”, Neurostimulation: An Overview: 207-212, 1985 by Lazorthes, Y and Upton, A.) Others had previously shown, in a double blind study, the efficacy of cerebellar stimulation for spasticity (see, e.g., McLellan, D et al., “Time course of clinical and physiological effects of stimulation of the cerebellar surface in patients with spasticity”, Journal of Neurology 41, 150-160, 1978).
Bilateral DBS
It has recently been demonstrated that Bilateral DBS of the internal pallidum and the subthalamic nucleus improves a number of aspects of motor function, movement time, and force production, with few significant differences between internal pallidum and subthalamic nucleus groups; and that the effects are similar to unilateral pallidal lesions reported elsewhere (see, Brown, R. G. et at, “Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease”, Annals of Neuology, 45(4)473-487, April 1999.) One year earlier, in 1998, R Kumar reported on one of the few double blind studies that objectively verified the clinical effects of subthalamic nucleus (STN) DBS in advanced Parkinson's Disease (PD) (see Kumar, R, et. al., “Double-blind evaluation of subthalamic nucleus deep brain stimulation in advanced Parkinson's disease”, Neurology, 51:850-855, 1988). Kumar's conclusions were that STN DBS is a promising option for the treatment of advanced PD and that the clinical benefits obtained outweighed the adverse effects. Later, Kumar also looked at bilateral globus pallidus internus (GPi) DBS for medication-refractory idiopathic generalized dystonia, and reported obtaining good results (see, Kumar et al., “Globus pallidus deep brain stimulation for generalized dystonia: clinical and PET investigation”, Neurology, 53:871-874, 1999).
It has also been demonstrated that bilateral DBS in levodopa-responsive patients with severe motor fluctuations was safe and efficient (see, Ghika, J. et al., “Efficiency and safety of bilateral contemporaneous pallidal stimulation (deep brain stimulation) in levodopa-responsive patients with Parkinson's disease with severe motor fluctuations: a 2-year follow-up review”, J. Neurosurg., Vol. 89, pp713-718, November 1998). In this report, Ghika indicated that improvements in motor score Activities of Daily Living (ADL) were obtained, and that off time persisted beyond two years after the operation, but that signs of decreased efficacy started to be seen after 12 months. Siegfried, J confirmed in 1994 that the use of bilateral DBS for PD was both nondestructive and reversible (Siegfried, J. et al., “Bilateral chronic electrostimulation of ventroposterolateral pallidum: a new therapeutic approach for alleviating all Parkinsonian symptons”, Neurosurgery, 35(6):1126-1130, December 1994).
Unilateral DBS
Good results have also been demonstrated with unilateral thalamic DBS for refractory essential (ET) and Parkinson's Disease (PD) tremor, with 83% and 82% reductions respectively in contralateral arm tremor (see, Ondo W, et al., “Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson's disease tremor”, Neurology, 51:1063-1069, 1998). However, no meaningful improvement in other motor aspects was observed.
Unilateral and Bilateral Pallidotomy
In 1998, the results of unilateral ventral medial pallidotomy was reviewed in 22 patients at 3 months postoperatively and at 14 months (see, Schrag A, et al., “Unilateral pallidotomy for Parkinson's disease: results after more than 1 year”, J. Neurol Neurosurg Psychiatry, 67:511-517, 1999). It was concluded that the beneficial effects persist for at least 12 months, and that dyskinesias are most responsive to this procedure. The reduction of contralateral dyskinesias was, however, slightly attenuated after 1 year. Another study, involving 21 patients, demonstrated that the pain associated with PD can be significantly reduced with unilateral pallidotomy (see, Honey et al., “Unilateral pallidotomoy for reduction of Parkinsonian pain”, J Neurosurg. 91:198-201, 1999). Earlier, other researchers had demonstrated control of levodopa-induced dyskinesias by thalamic lesions delivered by microelectrode technique and controlled in size and accurately located with respect to ventralis oralis (Vo) complex and ventralis intermediate nucleus (Vim) (see, Narabayashi, et al., “Levodopa-induced dyskinesia and thalamotomy”, J. Neurology, Neurosurgery, and Psychiatry 47:831-839, 1984).
R M Scott et al. (Scott et al., “The effect of thalamotomy on the progress of unilateral Parkinson's disease”, J Neurosurg, 32:286-288, March 1970) reviewed 72 patients exhibiting long term post unilateral thalamotomy to determine whether the procedures were adequate. Their results indicated, as suggested previously by Cooper, that unilateral procedures were inadequate and that when symptoms were absent from the side not receiving the procedure, they often appeared later when they were no longer benign. E Levita (Levita et al., “Psychological comparison of unilateral and bilateral thalamic surgery”, Journal of Abnormal Psychology 72 (3), 251-254, 1967) reported no significant differences between unilateral versus bilateral thalamic surgery in cognitive and perceptual functions and performance on visual and auditory tasks of recent recall.
DBS and Effects on Memory, Other Functions
One group of researchers suggested that in the application of chronic DBS of the left ventrointermediate (Vim) thalamic nucleus for the treatment of PD on semantic (verbal fluency and confrontation naming) and episodic (word list) memory tasks that DBS might interfere with access to episodic memory, but enhance access to semantic memory (see, Troster et al., “Chronic electrical stimulation of the left ventrointermediate (Vim) thalamic nucleus for the treatment of pharmacotherapy-resistant Parkinson's disease: a differential impact on access to semantic and episodic memory?”. Brain and Cognition, 38:125-149, 1998). Troseter et al., suggested that future studies look at effects of number and locations of electrodes. Earlier, it had been reported that thalamic stimulation and thalamotomy had been utilized to study the H reflex (Laitinen et al., “Effects of thalamic stimulation and thalamotomy on the H reflex”, Electroencephalography and Clinical Neurophysiology 28:586-591, 1970). Laitinen's report found that the H reflex was facilitated by repetitive stimulation of the contralateral VL, while coagulation of VL diminished the H reflex in half of the patients, suggesting that there are at least two different pathways from the VL area which facilitate the spinal motoneurone.
Another report indicated that in five PD patients with “freezing” gait and postural instability, chronic unilateral DBS of the STN resulted in effectively alleviating this gait with improvement in walking in all of the patients tested (see, Yokoyama et al., “Subthalamic nucleus stimulation for gait disturbance in Parkinson's disease”, Neurosurgery, 45(1):41-49, July 1999). STN stimulation was also reported by other researchers to alleviate akinesia and rigidity in PD patients (Pollak et al., “Subthalamic nucleus stimulation alleviates akinesia and rigidity in Parkinsonian patients”, Adv Neurology, 69:591-594, 1996).
Pain, Device Failures, Issues in Implementing the Technology
It has been reported that parafasicular-center median nuclei stimulation for intractable pain and dyskinesia and thalamic stimulation for chronic pain have been successful. (Andy O J, “Parafascicular-center median nuclei stimulation for intractable pain and dyskinesia (painful-dyskinesia)”, Appl. Neurophysiol., 43:133-144, 1980; Dieckmann et al., “Initial and long-term results of deep brain stimulation for chronic intractable pain”, Appl. Neurophysiol., 45:167-172, 1982). Additionally, the notion of two separate sensory modulating system was supported through the combined stimulation of the periaqueductal gray matter and sensory thalamus (Hosobuchi, Y “Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus”, Applied Neurophysiology 46:112-115, 1983).
G H Duncan (Duncan et al., “Deep brain stimulation: a review of basic research and clinical studies”, Pain 45:49-59, 1991) reviewed 30 years of DBS for pain and concluded that there is considerable evidence, in both basic and clinical studies, suggesting that deep brain stimulation can modify the activity of nociceptive neurons, and that this approach should be a feasible alternative for the treatment of chronic, intractable pain. Duncan suggested that future research be constrained to primates, rather than in cats and rats to narrow the differences between basic and clinical studies and that overall, studies with mixed results appear to have poor controls without the benefit of rigorous experimental standards.
K. Kumar (Kumar et al., Deep brain stimulation for intractable pain: a 15-year experience”, Neurosurgery, 40(4):7360747, 1997) followed 68 patients over 15 years and noted long term effective pain control with few side effects or complications. R. R. Tasker (Tasker et al., “Deep brain stimulation for neuropathic pain”, Stereotack Funct. Neurosurg., 65:122-124, 1995) investigated the use a commercially-available electrode and stimulator, available from a well-known medical equipment manufacturer, for DBS for the treatment of pain. In his investigation, 62 patients were tested, and 25 patients implanted of paresthesia-producing (PP) and periventricular gray (PVG) were evaluated. In no case did PVG DBS produce pain relief: in 15 PP patients, some pain relief was produced. Of particular note were the problems associated with the use of the device: 2 cases of seizures due to migrated electrodes, 14 other electrode migrations, 2 receiver migrations, 1 receiver malfunction and 8 general equipment breakages, disconnections or extrusions.
R. M. Levy (Levy et al., “Treatment of chronic pain by deep brain stimulation: long term follow-up and review of the literature”, Neurosurgery, 21:6, 885-893, 1987) reported on the long term follow-up of treatment of chronic pain with DBS of 141 patients having a mean length of follow-up of 80 months post implant. Technical problems most often encountered included migration of the implanted electrodes and equipment failure that led to leakage of current and ineffective stimulation. Lasting relief from pain was obtained in 47% of patients with deafferentiation and 60% with nociceptive pain. Caparros-Lefebvre (Caparros-Lefebvre et al., “Improvement of levodopa induced dyskinesias by thalamic deep brain stimulation is related to slight variation in electrode placement: possible involvement of the centre median and parafascicularis complex”, J. Neurol. Neurosurg. Psychiatry, 67:308-314, 1999) investigated why two teams using the same procedure and the same target for DBS obtained different results on levodopa induced dyskinesias, whereas Parkinsonian tremor was improved or totally suppressed, and it was discovered that there was on average electrode placement difference of 2.9 mm in electrode depth, which did not seem to correspond to the coordinates of the VIM, but rather seemed to be closer to those of the centre median and parafascicularis (CM-Pf) complex. The Caparros-Lefebvre study seems to support the hypothesis that patients experiencing an improvement of dyskinesias under DBS are actually stimulated in a structure which is more posterior, more internal and deeper than the VIM, very close to the CM-Pf. However, J. Guridi (Guridi et al., “Stereotactic targeting of the globus pallidus internus in Parkinson's disease: imaging versus electrophysiological mapping”, Neurosurgery, 45(2):278-289, August, 1999) determined that lesion targeting based on MRI alone is not sufficiently accurate to guarantee placement of the lesion in the sensorimotor region of the globus pallidus internus (Gpi).
J. Miles (Miles et al., “An electrode for prolonged stimulation of the brain”, Applied Neurophysiology 45:449-455, 1982) described several of the problems with the electrode used in the Kumar study: 1) electrode roughness presents a danger of trauma along the cannula track; 2) definite risk of early displacement of the electrode tip from its target site, especially with the electrode is disengaged from the insertion tool, because the intrinsic springlike behavior of the electrode tends to cause it to retract along its insertion track; 3) displacement of the electrode tip from its insertion position can also occur over a period of time, presumably due to the dynamic pulsatile nature of the brain; 4) repositioning of an electrode which is not producing satisfactory stimulation effects is difficult because of the progressively increasing distortion and springlike behavior of the electrode; and 5) the electrodes are expensive. Miles went on to describe an electrode with a feature that would allow it to be anchored at the insertion target location thus preventing movement post insertion. J Siegfried (Siegried et al., “Intracerebral electrode implantation system.” Journal of Neurosurgery 59:356-359, 1983) also described an improved electrode along with a fixation device which could secure the electrode leadwire accurately with a fixture at the burr hole location.
DBS and Essential Tremor
R. Tasker ((Tasker “Deep brain stimulation is preferable to thalamotomy for tremor suppression”, Surg. Neurol., 49:145-154, 1998) demonstrated that DBS is preferable to thalamotomy for tremor suppression in that tremor recurrence after DBS can be controlled by stimulation parameter adjustment rather than by re-operation, but thalamotomy recurrence can only be corrected by secondary surgery. Additionally, ataxia, dysarthria and gait disturbance were more common after thalamotomy (42%) than in DBS (26%) and that when they occurred after DBS they were nearly always controlled by adjusting stimulation parameters. J P Hubble (Hubble et al., “Deep brain stimulation for essential tremor”, Neurology, 46:1150-1153, 1996) demonstrated that DBS applied in the left Vim thalamic nucleus could be applied for essential tremor (ET) safely and effectively.
Upper Limb
R. G. Brown (Brown, et al., “Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease”, Annals of Neurology, 45(4)473-487, April 1999) has also shown that upper limb akinesia in Parkinson's disease may be treated by DBS of the internal pallidum or subthalamic nucleus.
Basic Research
R. Iansek (Iansek et al., “The monkey globus pallidus: neuronal discharge properties in relation to movement”, Journal of Physiology 301:439-455, 1980) demonstrated that the function of pallidal neurones is intimately concerned with movement performance, as very discrete movements were represented by the discharges of individual neurons. A Benazzouz (Benazzouz et al., “Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: electrophysiological data”. Neuroscience Letters, 189:77-80, 1995) demonstrated that high frequency stimulation of the subthalamic nucleus (HFS-STN) induces a cl73 ear cut decrease in neuronal activity in its two main efferents, the substantia nigra pars reticulata (SNr) and entopeduncular nucleus (EP) in basic studies in rats, thus providing an explanation for the alleviation of Parkinsonian symptoms by chronic STN stimulation in human patients.
R R Tasker (Tasker et al., “Investigation of the surgical target for alleviation of involuntary movement disorders”, Appl. Neurophysiol., 45:261-274, 1982) reviewed data from 198 stereotactic procedures with data from 9,383 sites, concluding that a common target in inferior VIM in the 13.5 mm sagittal plane for the control of a variety of dyskinesias existed.
From the above brief review of the literature, it is thus seen that although much research has been done to date, there exists a critical need in the art for a DBS system that can specifically address the needs of individual patients in order to provide relief or treatment for various disorders.